Postpartum MDMA Co-occurring PTSD and OUD

• Status: Not yet recruiting
• Trial end date: 2024-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

This is an open-label study of the use of MDMA Assisted Therapy for postpartum people with co-occurring Post Traumatic Stress Disorder (PTSD) and Opioid Use Disorder (OUD). The study protocol has been adapted from the Phase 3 studies sponsored by the Multidisciplinary Association for Psychedelic Studies (MAPS) for PTSD. Due to the high rate of concurrence of PTSD and OUD, people with OUD may experience great benefit from the treatment of their PTSD with MDMA-assisted therapy based on the phase 2 and 3 studies for PTSD. Use of MDMA-assisted therapy in this population has the potential to be of benefit for their OUD and maternal- infant attachment.

This study will serve to explore the feasibility and safety of offering MDMA-assisted therapy for treatment of PTSD in postpartum people with opioid use disorder. The CAPs 5 (PTSD) is the primary outcome, the Timeline Follow-Back (TLFB) for opioid use is the secondary outcome and other assessments of opioid use disorder, effects on maternal-infant attachment, social connectedness and other mental health outcomes are exploratory. The study will be conducted at the University of New Mexico Health Sciences Center located in Albuquerque New Mexico. In addition to northern New Mexico being an epicenter of the current opioid use disorder epidemic in the United States there is a long-standing history of multigenerational use of illicit opioids in many communities of northern New Mexico. There are high rates of opioid use disorder on pregnancy and accompanying Neonatal Opioid Use Withdrawal Syndrome (NOWS) in Albuquerque, Santa Fe, and surrounding communities.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of New Mexico

Criteria

Inclusion Criteria:

• Potential participants are eligible to enroll in the protocol if they:

1. Are at least 18 years old.

2. Have opioid use disorder and are using daily oral methadone or sublingual buprenorphine (or buprenorphine with naloxone in 4:1 ratio) of 24 mg or less. Assessed as stable for at least 3 months based upon review of the University of New Mexico Milagro and FOCUS program medical records or direct communication with the participant's buprenorphine or methadone prescriber.

3. Are fluent in speaking and reading English. This criteria is needed as the protocol requires two therapists that have specific training and it would be very difficult to identify two therapists fluent in another language

4. Are able to swallow pills.

5. Agree to have study visits recorded, including Experimental Sessions, Independent Rater assessments by an on-site Independent Rater for CAPS-5, and non-drug therapy sessions.

6. Must provide a contact (relative, spouse, close friend or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.

7. Must agree to inform the investigators within 48 hours of any medical conditions and procedures.

8. If able to become pregnant, must have a negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e., condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom). Not able to become pregnant is defined as permanent sterilization or postmenopausal.

9. Agree to the lifestyle modifications described in Section 3.0 above:

Medical History

10. At Screening, meet DSM-5 criteria for current moderate to severe PTSD with a symptom duration of 6 months or longer.

11. At Screening, meet DSM-5 criteria for Opioid Use Disorder.

12. At Screening, have had PTSD symptoms for at least three months and at least moderate PTSD symptoms in the last month based on PCL-5 total score of 40 or greater.

13. May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease

14. May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.

15. At Baseline, have at least moderate PTSD per CAPS-5 and symptoms in the last month constituting a CAPS-5 Total Severity Score of 28 or greater

16. May have current mild alcohol or cannabis use disorder (meets 2 or 3 of 11 diagnostic criteria per DSM-5) or moderate alcohol or cannabis use disorder in early remission for the 3 months prior to enrollment (meets 5 of 11 diagnostic criteria per DSM-5).

17. May have a history of or current Diabetes Mellitus (Type 2) if additional screening measures rule out underlying cardiovascular disease, if the condition is judged to be stable on effective management, and with approval by the study physician.

18. May have hypothyroidism if taking adequate and stable thyroid replacement medication.

19. May have a history of, or current, glaucoma if approval for study participation is received from an ophthalmologist.

Exclusion Criteria:

• Potential participants are ineligible to enroll in the protocol if they:

1. Are not able to give adequate informed consent.

2. Prisoners will be excluded

3. Are likely, in the investigator's opinion and via observation during the Preparatory Period, to be re-exposed to their index trauma, lack social support, or lack a stable living situation.

4. Have used Ecstasy (material represented as containing MDMA at least once within 6 months of the first Experimental Session; or have previously participated in a MAPS-sponsored MDMA clinical trial.

5. Have any current problem which, in the opinion of the investigator or study physician, might interfere with participation.

6. A 12 Lead EKG demonstrates QTc greater than 460 msec at time of screening for any potential participant or for the participants using methadone on an EKG obtained within 72 hours of each MDMA treatment session. An abnormal EKG may be repeated once to confirm the presence of QTc prolongation. 460 msec used as the upper acceptable limit as this study only includes women and the level of QTc that is considered abnormal is 10-20 msec longer for women.

Psychiatric History

7. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.

8. Have a history of or a current primary psychotic disorder, bipolar disorder 1 assessed via MINI and clinical interview or dissociative identity disorder assessed via structured clinical interview (SCID).

9. Have a current eating disorder with active purging assessed via MINI and clinical interview.

10. Have current major depressive disorder with psychotic features assessed via MINI.

11. Have a current moderate (not in early remission in the 3 months prior to enrollment based on meeting 4 or 5 of 11 diagnostic criteria per DSM-5) or severe alcohol or cannabis use disorder within the 6 months prior to enrollment (meets at least 6 of 11 diagnostic criteria per DSM-5).

12. Have an active illicit (other than cannabis or opioids) or prescription drug substance use disorder at any severity within 3 months prior to enrollment.

13. If there has been a diagnosis of moderate or severe cannabis use disorder within the last six months prior to enrollment, then the participant will need to have tapered off cannabis prior to the time of enrollment in the study and have either entered abstinence, limited cannabis use, or mild cannabis disorder. Mild cannabis use disorder or cannabis use alone are not exclusion criteria, however there can be no use in the 24 hours prior to the medication session.

14. Have current Personality Disorders Cluster A (paranoid, schizoid, schizotypal),) assessed via SCID-5-PD

15. Investigators will exclude potential participants with high risk of adverse emotional or behavioral reaction based on investigator's clinical evaluation (e.g., evidence of serious personality disorder, antisocial behavior, serious current stressors, or lack of meaningful social support)

16. Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior, in the judgment of the investigator, will not be enrolled. Any participant presenting with the following on the Baseline C-SSRS will be excluded:

• Suicidal ideation score of 4 or greater within the last month of the assessment at a frequency of once a week or more

• Suicidal ideation score of 5 within the last 6 months of the assessment

• Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study physician.

16. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist.

17. Require ongoing concomitant therapy with a psychiatric medication with exceptions described in Section 12.0: Concomitant Medications.

Medical History

18. Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, or aneurysm. Participants with other mild, stable chronic medical problems may be enrolled if the study physician and CI agree the condition would not significantly increase the risk of MDMA administration or be likely to produce significant symptoms during the study that could interfere with study participation or be confused with side effects of the Investigational Medicinal Product (IMP). Examples of stable medical conditions that could be allowed include, but are not limited to Diabetes Mellitus (Type 2), Human Immunodeficiency Virus (HIV) infection, Gastroesophageal Reflux Disease (GERD), etc. Any medical disorder judged by the investigator to significantly increase the risk of MDMA administration by any mechanism would require exclusion.

19. Have uncontrolled essential hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury [mmHg] or higher assessed on three separate occasions).

20. Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.

21. Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.

22. Have a history of arrhythmia, other than occasional premature atrial contractions (PACs) or PVCs in the absence of ischemic heart disease, within 12 months of screening. Participants with a history of atrial fibrillation, atrial tachycardia, atrial flutter or paroxysmal supraventricular tachycardia or any other arrhythmia associated with a bypass tract may be enrolled only if they have been successfully treated with ablation and have not had recurrent arrhythmia for at least one year off all antiarrhythmic drugs and confirmed by a cardiologist.

23. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

24. Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. Refer to Protocol Section _12___: Concomitant Medications.

25. Have symptomatic liver disease or have significant liver enzyme elevations. 26. Have history of hyponatremia or hyperthermia. 28. Weigh less than 48 kilograms (kg). 29. Are pregnant or are able to become pregnant and are not practicing an effective means of birth control.

30. If nursing, participant must agree to not breastfeed for 48 hours after ingestion of the final dose of MDMA during an experimental session. People may "pump and dump" during this time to maintain production.

31. Have engaged in ketamine-assisted therapy or used ketamine within 12 weeks of enrollment.